An NF-kappaB- and IKK-Independent Function of NEMO Prevents Hepatocarcinogenesis by Suppressing Compensatory Liver Regeneration.

The IκBKinase (IKK) complex represents a central signaling nexus in the TNF-dependent activation of the pro-inflammatory NF-κB pathway. However, recent studies suggested that the distinct IKK subunits (IKK, IKK, and NEMO) might withhold additional NF-κB-independent functions in inflammation and cancer. Here, we generated mice lacking all three IKK subunits in liver parenchymal cells (LPC) (IKK//NEMO) and compared their phenotype with mice lacking both catalytic subunits (IKK/), allowing to functionally dissect putative I-κB-Kinase-independent functions of the regulatory subunit NEMO.

New excavations at the HWK EE site: Archaeology, paleoenvironment and site formation processes during late Oldowan times at Olduvai Gorge, Tanzania.

This paper reports the results of renewed fieldwork at the HWK EE site (Olduvai Gorge, Tanzania). HWK EE is positioned across the boundary between Lower and Middle Bed II, a crucial interval for studying the emergence of the Acheulean at Olduvai Gorge. Our excavations at HWK EE have produced one of the largest collections of fossils and artefacts from any Oldowan site, distributed across several archaeological units and a large excavation surface in four separate trenches that can be stratigraphically correlated.

Site formation processes of the early Acheulean assemblage at EF-HR (Olduvai Gorge, Tanzania).

This paper investigates the formation history of the early Acheulean site of EF-HR (Olduvai Gorge, Tanzania). Our study focuses on the main site (T2-Main Trench) and adjacent trenches (T12 and T9), which constitute the bulk of the archaeological assemblage recently excavated in the EF-HR area (de la Torre et al., 2018a).

Noninvasive markers of liver fibrosis: on-treatment changes of serum markers predict the outcome of antifibrotic therapy.

Aim: The utility of noninvasive serum markers to longitudinally monitor liver fibrosis is not established.

Methods: A total of 70 patients with chronic hepatitis C who had previously failed antiviral therapy were randomized to receive pegylated interferon with or without silymarin for 24 months. Enhanced Liver Fibrosis (ELF) tests (hyularonic acid, terminal peptide of procollagen III, tissue inhibitor of matrix metaloproteinase-1) were performed on patient sera obtained before, during and at the end of the study (0, 12, 24 months) and liver histology obtained before and at the end of the study.

Biomarkers of Hepatic Fibrosis in Chronic Hepatitis C: A Comparison of 10 Biomarkers Using 2 Different Assays for Hyaluronic Acid.

Background: Advancing fibrosis is regarded as the most important factor when stratifying patients with chronic hepatitis C for retreatment.

Goals: (1) To compare the performance of 10 biomarkers of fibrosis, including patented tests, among patients with chronic hepatitis C and treatment failure; and (2) to assess the impact on biomarker performance of using 2 different assays of hyaluronic acid (HA).

Study: For 80 patients, liver histology (Metavir) was compared with biomarker scores using sera obtained within 6 months of liver biopsy (indirect biomarkers: AST:ALT ratio, APRI, Forns index, FIB-4, Fibrometer V3G; direct biomarkers: ELF, Fibrospect II, Hyaluronic acid-HA, Fibrometer V2G, Hepascore).

Incidental genetic findings in randomized clinical trials: recommendations from the Genomics and Randomized Trials Network (GARNET).

Recommendations and guidance on how to handle the return of genetic results to patients have offered limited insight into how to approach incidental genetic findings in the context of clinical trials. This paper provides the Genomics and Randomized Trials Network (GARNET) recommendations on incidental genetic findings in the context of clinical trials, and discusses the ethical and practical issues considered in formulating our recommendations. There are arguments in support of as well as against returning incidental genetic findings in clinical trials.

Critical review of the use of erythropoietin in the treatment of anaemia during therapy for chronic hepatitis C.

Combined pegylated interferon (PegIFN) and ribavirin represents the standard therapy for patients with chronic hepatitis C (CHC), which allows for sustained viral response (SVR) in up to 90% of patients depending on certain viral and host factors. Clinical studies have demonstrated the importance of adherence to therapy, that is, the ability of patients to tolerate and sustain a fully dosed therapy regimen. Adherence is markedly impaired by treatment-related adverse effects.

zucchini and squash encode two putative nucleases required for rasiRNA production in the Drosophila germline.

RNAi is a widespread mechanism by which organisms regulate gene expression and defend their genomes against viruses and transposable elements. Here we report the identification of Drosophila zucchini (zuc) and squash (squ), which function in germline RNAi processes. Zuc and Squ contain domains with homologies to nucleases.

Deadlock, a novel protein of Drosophila, is required for germline maintenance, fusome morphogenesis and axial patterning in oogenesis and associates with centrosomes in the early embryo.

The deadlock gene is required for a number of key developmental events in Drosophila oogenesis. Females homozygous for mutations in the deadlock gene lay few eggs and those exhibit severe patterning defects along both the anterior-posterior and dorsal-ventral axis. In this study, we analyzed eggs and ovaries from deadlock mutants and determined that deadlock is required for germline maintenance, stability of mitotic spindles, localization of patterning determinants, oocyte growth and fusome biogenesis in males and females.

A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation.

Iron absorption by the duodenal mucosa is initiated by uptake of ferrous Fe(II) iron across the brush border membrane and culminates in transfer of the metal across the basolateral membrane to the portal vein circulation by an unknown mechanism. We describe here the isolation and characterization of a novel cDNA (Ireg1) encoding a duodenal protein that is localized to the basolateral membrane of polarized epithelial cells. Ireg1 mRNA and protein expression are increased under conditions of increased iron absorption, and the 5' UTR of the Ireg1 mRNA contains a functional iron-responsive element (IRE).

Specific isoforms of squid, a Drosophila hnRNP, perform distinct roles in Gurken localization during oogenesis.

Heterogeneous nuclear RNA-binding proteins, hnRNPs, have been implicated in nuclear export of mRNAs in organisms from yeast to humans. A germ-line mutation in a Drosophila hnRNP, Squid (Sqd)/hrp40, causes female sterility as a result of mislocalization of gurken (grk) mRNA during oogenesis. Alternative splicing produces three isoforms, SqdA, SqdB, and SqdS.

Ribosomal pausing and scanning arrest as mechanisms of translational regulation from cap-distal iron-responsive elements.

Iron regulatory protein 1 (IRP-1) binding to an iron-responsive element (IRE) located close to the cap structure of mRNAs represses translation by precluding the recruitment of the small ribosomal subunit to these mRNAs. This mechanism is position dependent; reporter mRNAs bearing IREs located further downstream exhibit diminished translational control in transfected mammalian cells. To investigate the underlying mechanism, we have recapitulated this position effect in a rabbit reticulocyte cell-free translation system.

Binary specification of nonsense codons by splicing and cytoplasmic translation.

Premature translation termination codons resulting from nonsense or frameshift mutations are common causes of genetic disorders. Complications arising from the synthesis of C-terminally truncated polypeptides can be avoided by 'nonsense-mediated decay' of the mutant mRNAs. Premature termination codons in the beta-globin mRNA cause the common recessive form of beta-thalassemia when the affected mRNA is degraded, but the more severe dominant form when the mRNA escapes nonsense-mediated decay.

Abnormal localization of iron regulatory protein in Alzheimer's disease.

A role for altered iron metabolism in the pathogenesis of Alzheimer's disease has been suggested by several reports associating the cardinal neuropathologic lesions with markers of free radical-induced damage and redox-active iron. We hypothesized that the abnormal distribution of iron in Alzheimer brain might result from alterations in iron regulatory proteins (IRP) such as IRP-1 and IRP-2, the main control elements of cellular iron homeostasis. Here, we report that while IRP-1 is present at similar levels in both Alzheimer and control brain tissue, IRP-2 shows striking differences and is associated with intraneuronal lesions, including neurofibrillary tangles, senile plaque neurites and neuropil threads.

Myocyte-specific enhancer binding factor 2C expression in fetal mouse brain development.

We have previously found that myocyte-specific enhancer binding factor 2C (MEF2C) is expressed in the brain, where it is found at high levels in the developing cerebral cortex. We have now examined MEF2C expression in fetal mouse brain by in situ hybridization and by immunohistochemistry from E11 to E17, the period when most cortical neurons are born. The distribution of MEF2C mRNA detected by in situ hybridization closely resembles that of MEF2C immunoreactivity.

Identification of four genomic loci highly related to casein-kinase-2-alpha cDNA and characterization of a casein kinase-2-alpha pseudogene within the mouse genome.

Using the coding region of the human CK-2 alpha cDNA as a probe for screening a genomic mouse library, positive clones representing four different genomic loci were isolated. Partial DNA sequences of these loci encompassing the first 120 nucleotides of the putative coding region are reported. One positive clone was further analyzed by sequencing a 3.

[Analysis of regional trends in narcotic studies between 1980 and 1986].

During the period of survey, the number of narcotic drug seizures by the law, especially cannabis resin, has increased considerably. The details on this development are presented. The following main analytical results were obtained: the median concentration of THC in cannabis resin has increased up to 8.

[Perfected, professional body-packing].

A 27-year-old Columbian male was arrested in Aix la Chapelle at the border to Belgium, as he was suspected, of smuggling drugs in his body. Ultrasonographic and radiographic examinations revealed numerous packets in the colon descendens and the ampulla recti. After administration of laxatives, 70 packets were excreted that had been swallowed 3 days before in Bogota, Columbia.

[Toxic environmental factors in sudden infant death (SIDS)].

The increasing number of discussions on the influence of toxic environmental factors, including SIDS, prompted systematic postmortem chemical-toxicological investigations to be carried out on 54 SIDS cases and 2 control cases of the same age group. Tissue levels of arsenic, lead, cadmium, mercury, and pentachlorphenol, as well as other organic noxious agents, were measured in several organs. In addition, the COHb concentrations were determined.

[Detection of E 605 several years after burial].

Five cadavers were exhumed 8 months to 20 years after burial, as it was suspected that these persons had been poisoned with E 605. Parathion at doses of between 200 mg and 500 mg might have been administered. Parathion, aminoparathion, paraoxon, p-nitrophenol, and a decomposition product of CI solvent blue 78 (Ceresblau) were found 9 months after burial, and aminoparathion and p-nitrophenol could be detected 3 and 7 years after burial.